Uncovering the role of microbiota-derived metabolites in the initiation and progression of pancreatic cancer

• Applicant: Dr. Joseph Tintelnot
• Subject Area: Gastroenterology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553260309

The prognosis for individuals diagnosed with pancreatic cancer is grim, as most patients either present with advanced-stage disease initially or experience disease relapse after successful tumor removal, rendering pancreatic cancer one of the most lethal forms of cancer. Both my preliminary data and findings from other research teams suggest that the intestinal microbiota, comprising all bacteria, fungi, and viruses inhabiting our intestines, may play a role in initiating and advancing pancreatic ductal adenocarcinoma (PDAC). Our daily dietary choices exert a significant influence over the composition of our microbiota. However, they also have the potential to impact and regulate the metabolic byproducts produced by these microorganisms. These metabolic byproducts manifest as small molecules known as metabolites, which can permeate the mucosal tissue of the gastrointestinal tract to enter the bloodstream, thereby influencing our immune system and potentially even cancer cells. Nonetheless, whether these metabolites could potentially contribute to driving the progression of PDAC remains an unanswered question. In this study, we will analyze the microbiota and microbiota-derived metabolites of patients suffering from various aggressive forms of PDAC to determine which of these metabolites are associated with more aggressive or moderate PDAC. Through in vitro and in vivo experiments, we will investigate whether these metabolites indeed promote the advancement of PDAC. Once a connection between metabolites and PDAC progression is established, whether by directly affecting cancer cells or indirectly through the immune system, we will explore microbiota-targeted interventions. This includes examining diets that can alter the microbiota or modify its metabolic output to potentially slow down PDAC progression. The ultimate goal of this translational project is to uncover new mechanisms that could be targeted for future treatments, with the aim of improving the prospects for individuals with PDAC.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: LC/MS
• Instrumentation Group: 1700 Massenspektrometer